Disclosure
The practice of medicine has become progressively more sophisticated. Physicians can now achieve the goal of facilitating the healing process while simultaneously minimizing or even eliminating the pain once thought necessary to achieve this goal. Adults were the first to benefit from these advances. Only within the last 2 decades has the sophisticated medical establishment realized that pediatric patients, including neonates, also feel pain and require medical intervention to alleviate unnecessary suffering. Beliefs of caregivers substantially affect medical intervention to alleviate unnecessary suffering. Before the late 1980s and early 1990s, a common belief was that neonates experienced no pain or less pain than adults, children, or infants who underwent similar surgical procedures. A healthcare provider who believes that neonates feel little pain tends to observe few clinical signs of pain in neonates. Furthermore, such practitioners tend to believe that narcotic administration is associated with increased risk in neonates. Although these practitioners may administer narcotic analgesics, they use frequently nonaggressive intervention and subtherapeutic regimens in preverbal patients compared with adults A concern about respiratory depression is the most notable limitation to the administration of narcotics postoperatively, especially in nonintubated neonates or neonates undergoing minor surgical procedures. Although this concern may have some pharmacologic basis, it should not prevent the appropriate administration of narcotic analgesics to neonates who have undergone clinically significant surgery. Furthermore, other therapeutic regimens formerly reserved for adults, adolescents, and older children may also be used safely to manage postoperative pain in neonates. This article considers the application of medical advances in pain management to the care of our youngest perioperative patients—neonatal surgical patients. For excellent patient education resources, visit eMedicine's Public Health Center. Also, see eMedicine's patient education article Pain After Surgery.
Suffering is minimized during the preoperative visit when physicians avoid unnecessary laboratory studies, especially those that require phlebotomy. Furthermore, inappropriately long periods of taking nothing by mouth (NPO) can be eliminated to minimize patient discomfort. Postoperative pain management should be discussed when the neonate and family are examined preoperatively. Issues that may eventually affect decisions about postoperative pain management and should, therefore, be addressed include the patient's coexisting disease states, the surgical site, the patient's postoperative disposition, and the family consent's for pain-management techniques that are being considered. Neonates who are unstable, septic, or likely to remain intubated after surgery are frequently given narcotics during the procedure. These narcotics are continued as needed afterward. Narcotic administration is pursued cautiously in neonates who are postoperatively transferred to non-ICU settings. Neonates undergoing outpatient surgery or surgery associated with minor postoperative pain are frequently given acetaminophen with regional or local anesthetic infiltration after surgery. Neonates who undergo lower-extremity, abdominal, or thoracic surgery are excellent candidates for regional anesthesia, whether they are undergoing inpatient or outpatient surgery. As in adults, coexisting pulmonary disease in neonates may be an excellent reason to consider regional anesthesia for postoperative pain management. Finally, anxiety among family members concerning a pain-control strategy should be thoroughly addressed and considered in postoperative decision-making about pain management.
After extensive work in the 1980s and 1990s, the fact that neonates experience pain and mount a stress response was established and appreciated. Metabolic and hormonal indicators of the degree of stress a surgical patient has are monitored during and after surgery. These indicators are perioperatively elevated in neonates. Even premature neonates undergoing surgery can mounting a clinically significant stress response, as measured by using hormonal and metabolic indicators. Stress indicators include plasma adrenaline, noradrenaline, glucagon, insulin, and cortisol levels as well as blood glucose, lactate, pyruvate, and alanine concentrations. The mounting of a surgical stress response results in catabolic responses, including glycogenolysis, gluconeogenesis, and lipolysis during the perioperative period. These catabolic responses, when unmodulated by medical intervention, may have a detrimental effect on the clinical course of a neonatal surgical patient. Adverse circulatory and respiratory events are also most likely to occur during the postoperative course of neonates who have had inadequate interventions to minimize stress responses. Tachycardia, systemic hypertension, pulmonary hypertension, respiratory embarrassment, and intraventricular hemorrhage may be associated with inadequate pain control in neonates. Furthermore, inadequate treatment of pain may have implications that extend beyond the neonatal period, including hypersensitivity to noxious stimuli later in life. |
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Management of the surgical stress response in neonates can largely be accomplished with the same pharmacologic interventions as those used for anesthesia in other surgical patients. Volatile anesthetic agents are the most common means of providing intraoperative anesthesia and analgesia probably because they meet, at least to some degree, each of the criteria required for complete anesthesia, including some hypnosis, amnesia, analgesia, and muscle relaxation. Anand et al demonstrated that blood levels of hormonal and metabolic indicators of the stress response were lower in neonates who received volatile anesthetics during surgery than in those who did not (Anand, Br Med J (Clin Res Ed), 1988). Furthermore, clinical stability of neonates during and after surgery improved with the adequate administration of volatile anesthetic agents during surgery. The relative potency of each volatile anesthetic agent is measured in terms of the minimum alveolar concentration (MAC) of the inhaled agent at which 50% of patients do not have skeletal muscle movement in response to surgical incision or another noxious stimulus. The patient's age appears to influence the MAC of a given volatile anesthetic. Although the MAC is higher in infants than in any other age group, it may be 15-25% lower in neonates than in infants and even lower in premature neonates. Volatile anesthetics are potent myocardial depressants and vasodilators. As a consequence, systolic blood pressure and mean arterial blood pressure may decrease when these agents are administered. In some neonates, other analgesic agents may be used to decrease the requirement for volatile anesthetics during surgery to avoid some of the hemodynamic changes that may occur with the administration of these agents. In fact, surgical anesthesia can be accomplished without the use of any volatile anesthetic agents. Narcotics are not complete anesthetic agents, as they do not provide muscle relaxation or amnesia, which are essential functions of complete anesthetics. However, they are potent analgesic medications. In neonates, blood pressure may decrease less with intraoperative use of narcotics than with the administration of volatile anesthetics. Furthermore, narcotics are useful adjuncts to anesthetics based on volatile agents because they can reduce the requirement for volatile agent, reducing any hemodynamic lability. Narcotic-based anesthetics are commonly used during cardiovascular procedures in neonates. Physicians should note that the pharmacokinetics of narcotics administered to neonates differs from the pharmacokinetics of narcotics given to infants, children, and adolescents. Neonates lowered rate of clearance, increased volume of distribution, prolonged elimination half-life, and heightened plasma concentration after they receive boluses of narcotics. As a consequence, intraoperative use of narcotics may affect the postoperative disposition of neonates. Narcotics commonly used for intraoperative analgesia in neonates include morphine, fentanyl, sufentanil, and remifentanil. Ketamine, a phencyclidine derivative, produces amnesia and intense analgesia. This drug affects opioid receptors and N-methyl-D-aspartate (NMDA) receptors, as well as voltage-sensitive calcium ion channels as it induces its analgesic effects. Ketamine actually stimulates the cardiovascular system; therefore, it is frequently associated with increased systolic and mean arterial blood pressures and heart rate when administered intraoperatively. Although ketamine may not be associated with increased blood pressure in preterm neonates, it is associated with decreased mean arterial pressure and systolic blood pressures, though these decreases are smaller than those of the other analgesic medications commonly used during surgery. Beneficial effects of ketamine include bronchodilation and less depression of ventilation than that observed with other agents. Adverse effects in neonates include increased production of salivary and tracheobronchial secretions, cerebral vasodilation, and apnea in patients with increased intracranial pressure.
One factor that has contributed to inadequate pain management in neonates is the pervasive belief that neonates do not feel pain. This misconception is perpetuated, at least in part, by the conspicuous absence of adequate tools to assess pain levels in this patient population. To a large extent, pain assessment in patients older than neonates depends on their ability to report pain level in some form to the caregiver. When patients cannot express pain verbally, pain assessment depends more on evaluations by the caregiver than by the patient. Even when pain is evident, quantifying the level is not easy. An effective pain-assessment tool must enable healthcare providers to objectively quantify the patient's level of pain so that they can accurately measure the effectiveness of interventions designed to alleviate unnecessary suffering. Although no perfect tool exists for assessing pain in neonates, infants, and preverbal children, several useful tools are available. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) was one of the first observational pain scales. This tool includes the categories of (1) cry, (2) facial expression, (3) verbal response, (4) torso position, (5) leg activity, and (6) arm movement in relationship to the surgical wound. In general, each category is scored 0, 1, 2, or 3, with high scores indicating high pain levels, but the scale varies with each category evaluated. The CHEOPS was originally used to evaluate postoperative pain in children aged 1-7 years. Evaluators determined that it was both valid and reliable for assessing pain in this patient group. However, a pain-assessment tool that is appropriate for preverbal children may not be appropriate for neonates. Still, CHEOPS is a tool against which the validity of other pediatric pain-assessment tools can be measured. The Objective Pain Scale (OPS), which Hannallah et al developed, is both validity and reliability in pain assessment. The OPS is used to assess (1) blood pressure, (2) crying, (3) movement, (4) agitation, (5) posture, and (6) verbalization. Each parameter is scored 0, 1, or 2, with high scores indicating increased distress. This instrument is important because it includes a cardiovascular parameter in the assessment of postoperative pain. Many advocate use of cardiovascular parameters as the most objective measures of the pain response in preverbal children. However, their utility is limited because other causes of distress may dramatically change these parameters. Although cardiovascular parameters are insufficient as the sole means of assessing pain in this patient population, they may be helpful. However, the OPS, like the CHEOPS, has been used in mostly infants and children and not neonates. The COMFORT scale has been favorably received as a tool to assess postoperative pain in the neonatal population. This tool was originally developed to assess distress in ventilated patients in the pediatric ICU. However, the COMFORT scale was reliable and valid in assessing pain in postoperative patients in 1 large study in which pain was evaluated in 158 neonates along with older infants and children. The COMFORT scale comprises 6 behavioral items, namely, (1) alertness, (2) calmness, (3) muscle tone, (4) movement, (5) facial tension, and (6) respiratory response, and 2 physiologic items, namely, (1) heart rate and (2) mean arterial blood pressure. Each item is scored 1, 2, 3, 4, or 5, with a high score indicating increased distress. The additional variables assessed and the increased number of scores possible for each variable may make this tool more useful than others in identifying subtle changes in patient discomfort. On the other hand, the relative complexity of this scale may be a disadvantage in terms of its clinical utility. A fourth scale is the crying, requires oxygen, increased vital signs, expression, and sleeplessness (CRIES) scale. This tool may also be useful to assess the pain of neonates after surgery. This scale is designed to analyze 5 variables: (1) crying, (2) requirement of increased oxygen administration, (3) increased vital signs, (4) expression, and (5) sleeplessness. Each variable is scored 0, 1, or 2. This instrument has demonstrated validity, reliability, user friendliness, and acceptance as a tool to assess postoperative pain among neonatal intensive-care nurses. New tools are being developed and show promise in advancing the ability of healthcare providers to assess the pain experience of neonates. These tools include the Postoperative Pain Score, the Liverpool Infant Distress Scale, the Premature Infant Pain Profile, and the Neonatal Assessment of Pain Inventory. Each of the pain-assessment instruments discussed has strengths and limitations. For optimal use of any pain assessment tool, the physicians and neonatal nursing staff should select a tool, become familiar with its use, and systematically integrate its use into the institution's policies. This approach maintains the validity and reliability of the tool in measuring pain in neonates and allows for appropriate intervention to be undertaken, minimizing unnecessary postoperative suffering in neonatal patients.
After appropriate pain-assessment practices are established, the most formidable hindrance to alleviating postoperative pain in neonates is unfamiliarity with the safety and practicality of the options. Implementing an effective pain-management strategy in the neonatal surgical patient is a complex process. The strategy for pain management should begin during the preoperative assessment and continue with the intraoperative anesthetic management, as formerly discussed. Furthermore, the physician responsible for pain management must be aware that such care affects other components of postoperative care. When treating pain in neonates, one must consider the pharmacodynamic and pharmacokinetic issues unique to the neonatal period, the severity of the surgical insult, the patient's coexisting diseases, the surgical site, the postoperative management plans of the surgeons and neonatal or pediatric physicians, and the neonate's postoperative disposition. Opioid administration remains the most common means of achieving pain control in surgical patients. Neonates who are expected to have moderate-to-severe postoperative pain are no exception. Opioids may be administered safely to neonates when a well-constructed pain-management plan is implemented. Although certainly not prohibitive, the risk of apnea cannot be ignored. As during the intraoperative period, more than 1 opioid may be considered to manage postoperative pain in the surgical neonatal patient. Fentanyl and morphine are the drugs most commonly selected when opioids are administered after surgery. Fentanyl Fentanyl is most appropriately administered by means of intravenous (IV) infusion to neonates who are ventilated preoperatively and who are expected to remain ventilated postoperatively. Episodes of apnea are more severe when this drug is administered as an IV bolus of 1-2 mcg/kg than when it is given as a continuous IV infusion of 1-2 mcg/kg/h. However, respiratory depression may be less problematic in infants than in neonates. Too-rapid bolus administration has been associated with acute rigidity of the chest wall that severely compromises ventilation of the patient. As with many other medications administered to neonates, the pharmacokinetics of fentanyl are highly variable. Of particular interest, the half-life of the drug may be prolonged in neonates who have increased abdominal pressure after surgery because of impaired hepatic blood flow. Fentanyl is less likely to cause hypotension than morphine; this feature may be a consideration in the postoperative neonate. Morphine Morphine remains the opioid analgesic most commonly used to control moderate-to-severe postoperative pain in neonates. Surgical procedures after which morphine is given may include craniotomy, thoracotomy, sternotomy, and laparotomy. Incremental IV boluses of 20 mcg/kg, not to exceed 100 mcg/kg, are typically administered for acute pain management in the postanesthesia recovery unit. When a continuous IV infusion is used for postoperative pain management in neonates, the initial rate varies depending on the patient's age. Initial IV infusion rates of 10 mcg/kg/h are acceptable for neonates younger than 1 week. Neonates older than 1 week tolerate 15 mcg/kg/h, whereas older infants may tolerate 20-40 mcg/kg/h. Supplemental IV boluses of up to 50 mcg/kg may be administered for episodes of breakthrough pain in neonates who are receiving morphine by means of continuous infusion. Respiratory responses to morphine do not differ in term neonates compared with infants and children when identical plasma levels of the drug are achieved and maintained. Increased caution may be advisable when morphine infusions are started in preterm neonates, who may require infusion rates significantly lower than those given to term neonates to achieve the same plasma levels of morphine. At steady-state plasma concentration >20 ng/mL, the likelihood of respiratory depression increases in all neonates. Practitioners who administer morphine infusions for postoperative pain control should be aware of the pharmacokinetic disadvantages that place neonates at risk for respiratory depression because of increased plasma concentrations. Neonates have immature hepatic enzyme systems, which may result in a doubling of the elimination half-life of morphine in neonates (ie, 10-20 h) compared with half-lives in infants (ie, 5-10 h). Low plasma protein levels in neonates may result raise levels of free drug and slower plasma clearance of morphine. Morphine clearance in neonates may be as little 50% of that of infants and 25% of that of adults. Furthermore, the rate of glucuronidation, the primary metabolic pathway of morphine, is slower in neonates than in infants and adults. Coexisting surgical and medical conditions may affect the pharmacokinetics of morphine in neonates. As mentioned before, abdominal surgery increased abdominal pressure postoperatively may impair drug metabolism or drug elimination, increasing the half-life of this drug. In addition, the pharmacokinetics of medications may be different in neonates with cardiac comorbidity than in those without congenital heart disease. Whether this change is secondary to impaired cardiac performance or abnormal circulatory dynamics on hepatic or renal function is unclear. Use of preservative-free morphine should also be considered because neonates are more susceptible than other patients to respiratory depression some preservatives cause. Morphine can also stimulate histamine release, resulting in systemic vasodilation. This characteristic may be either advantageous or disadvantageous to the postoperative neonate, and it should be considered when this drug is used. Meperidine Meperidine is seldom used for postoperative management of pain in neonates, though it can be administered in doses of 1 mg/kg. However, its pharmacokinetic profile dramatically varies in individual neonates. Furthermore, meperidine has epileptogenic metabolites, which tend to accumulate in patients with impaired renal function, as is inherent in the neonatal period. In the authors' opinion, the disadvantages of meperidine outweigh its advantages in the neonatal patient.
Nonnarcotic analgesics Nonnarcotic modalities are important in pain management in neonates who have undergone surgery. Acetaminophen is useful as a sole analgesic for mild discomfort or as an adjuvant medication for moderate-to-severe pain when narcotic or regional analgesia is used. Either oral or rectal administration may be chosen. Rectal administration is associated with low plasma levels and a prolonged elimination half-life. Although 15 mg/kg may be administered orally, this dose is associated with subtherapeutic plasma levels when administered rectally to neonates. An initial dose of 20-35 mg/kg is recommended for the initial preincision dose or for the immediate postoperative dose administered per rectum. In general, the risk-benefit profile for nonsteroidal anti-inflammatory drugs (NSAIDs) does not favor their use in neonates. Potential complications include renal toxicity, necrotizing enterocolitis, platelet dysfunction, and hemorrhage (particularly intracranial hemorrhage). In particular, the US Food and Drug Administration (FDA) has not approved ketorolac for use in neonates, and reports of its use in this patient population are absent from the literature. Moreover, ketorolac may be no more effective than high-dose rectally administered acetaminophen in some older patients. [Solutions of 25% sucrose administered orally have been shown in several studies of neonates to attenuate pain associated with noxious stimuli. Interestingly, administration of similar concentrations of glucose or dextrose has not demonstrated the same analgesic effects. Common regimens include administering up to 3 mL orally during painful procedures, such as heel stick and circumcision; some units allow for pacifiers dipped in a commercially available sucrose solution to calm infants at nursing discretion.] Sucrose 25% administered orally and repeatedly can blunt the pain response in neonates undergoing common but painful procedures such as circumcision, heel lancing, and venipuncture. Doses of 2-3 mL may be administered intraoperatively into the oral cavity by using a syringe or by using a pacifier dipped in the solution and then inserted into the patient's mouth. A commercially prepared solution is available, or it can be mixed at the bedside by using 1 packet of table sugar dissolved in 5 mL of water. Other sugars, such as dextrose and glucose, have not been shown to have the same analgesic effect. Nonpharmacologic interventions A discussion of nonnarcotic pain modalities is incomplete without a discussion of nonpharmacologic interventions. Although some form of these modalities may be used in older patients, they are considered central to the pain management of neonates. These modalities include bundling, holding, and rocking the neonate; provision of a pacifier to alleviate distress; and minimization of environmental stimuli, such as extraneous noise and unnecessary light.
Regional pain-control techniques are increasingly used to manage postoperative pain in neonates. Regional techniques may include single-dose administration of local anesthetics into the caudal space, plexus blockade of the upper or lower extremity, extrapleural catheter placement, or neuraxial catheter placement for continuous pain control after surgery. The most common regional techniques in neonates include single-dose caudal administration and placement of epidural catheters for prolonged pain management. Caudal anesthesia is a highly effective and simple technique associated with a high success and low complication rates. Caudal anesthesia is neuraxial anesthesia and therefore associated with some of the risks inherent to neuraxial access. However, because the neuraxial space is accessed at its most caudad entry point, the risk of neural injury or even inadvertent dural puncture is reduced. Sterile technique is required and may be accomplished by wearing sterile gloves or by palpating the caudal space anatomy through an alcohol swab (ie, the no-touch technique) before a single dose of medication is instilled into the caudal space. Use a short, beveled needle to minimize the likelihood of inadvertent intravascular or intramedullary injection of the local anesthetic. A caudal anesthetic can be successfully administered in 96% of pediatric patients. After the sacrococcygeal ligament is penetrated with the regional anesthetic needle, lower the angle of the needle, advance it no more than 3-5 mm, aspirate the syringe to ensure the absence of CSF or heme, and administer the local anesthetic. Bupivacaine remains the most commonly administered local anesthetic for single-dose caudal blocks. However, newer local anesthetics are being used with increasing frequency. Ropivacaine may offer distinct advantages over bupivacaine because it has a relatively benign cardiovascular toxicity profile. Levobupivacaine may offer the same advantage. The incidence of residual motor blockade is lower with both of the agents than with bupivacaine, without a diminishment of analgesic efficacy. Effective concentrations are 0.125-0.25% for bupivacaine, levobupivacaine, and ropivacaine. Volumes of 0.75-1 mL/kg and/or doses of up to 3 mg/kg are typically administered. Supplemental analgesics may not be required for as long as 12 hours after surgery when the caudal block is effective. Placement of a caudal, lumbar, or even thoracic catheter for continuous postoperative pain management has been proven safe and effective in neonates. An epidural catheter may be successfully placed by means of the caudal approach and advanced cephalad to the lumbar or thoracic level. By using superficial anatomic landmarks as a guide, the level of the catheter may be accurately predicted. This catheter may then be used for a postoperative infusion of narcotics or local anesthetics. Epidural catheters have been successfully used after many major neonatal surgical procedures that require laparotomy or thoracotomy, including hepatic resection and procedures to treat abdominal-wall defects (gastroschisis and omphalocele), tracheoesophageal fistula, congenital diaphragmatic hernia, and coarctation of the aorta. After successful catheterization and administration of an initial bolus through the epidural catheter, pain management may be maintained with a continuous infusion of analgesic medications. Epidural infusions are an acceptable alternative to the intermittent top-up technique. Epidural infusions are both safe and effective in term and preterm neonates. Postoperative epidural infusions of bupivacaine substantially reduce sedation and respiratory depression. Moreover, patients have improved oxygenation without the administration of supplemental oxygen with analgesia, complication rates, and hemodynamic profiles similar to that of patients who receive morphine infusions. In 1992, Berde reported recommendations to facilitate the safe use of epidural analgesia in pediatric patients after analyzing results in more than 20,000 pediatric regional anesthetic procedures at 15 institutions. Berde recommended that bolus dosing of epidural bupivacaine not to exceed 2-2.5 mg/kg. Infusion rates of 0.2-0.25 mg/kg/h were recommended for neonates. The report cautioned that children are probably not more resistant to local anesthetic toxicity than adults, as was previously thought. Neonates, in particular, may be at risk for local anesthetic toxicity because of diminished plasma levels of alpha1-acid glycoprotein, which could increase the free fraction and slower the clearance of bupivacaine. Premonitory symptoms or signs of local anesthetic toxicity may be absent in neonates. Reduce infusion rates for patients at risk for seizures. When the level of the epidural catheter is too low to provide adequate analgesia at the incision site in a neonatal patient, increasing the rate of the epidural infusion cannot safely overcome this problem. In 1 study, plasma levels of bupivacaine continued to increase and reached the upper limits of the safe range before the end of a 48-hour infusion period. In addition, plasma levels of bupivacaine rose in neonates who were at high risk for increased abdominal pressure after surgery. Furthermore, as with all drugs administered during the neonatal period, interindividual variability in plasma bupivacaine levels were considerable in neonates receiving epidural infusions. Although plasma clearance is lower in neonates than in adults who receive epidural infusions, this difference is especially dramatic in preterm neonates.
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